The determination of the mechanism of the neurotrophic actions of opioids is the broad goal of the ongoing research. The rat C6 glioma cell line will be used as an astrocytic model system. Recent evidence suggests that this cell line expresses at least two different opioid receptor types following treatment with desipramine (DMI). The receptors will be identified by northern blot analysis using radiolabeled intact mu, kappa and delta cDNAs. Addition of opioid agonist to DMI-treated C6 cells inhibits mitogen stimulated cell proliferation. Identification of the specific receptor(s) involved in the opioid inhibition of cell proliferation will be accomplished by using specific antagonists to each of the opioid receptors detected by northern blot analysis. Mitogen stimulation of C6 cells leads to an increase in the production of nitric oxide (NO) which has been positively correlated with an increase in cell proliferation. The ability of opioids to modulate NO production will be examined. The regulation of astrocyte proliferation in developing brain may prove to be a normal function of endogenous opioids in the control of cell numbers during ontogeny. Moreover, this effect of opioids on the fetus of drug-addicted mothers may contribute to the physiological and psychological delays observed in offspring. Finally, the role that opioids play in regulating gliogenesis may provide insight into mechanisms of neural regeneration after brain injury where astrocytic proliferation is prevalent.